A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly

IntroductionThis study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions.MethodsThis was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. C-max, AUC(0-t), and AUC(0-infinity) from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters.ResultsOf the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on C-max, AUC(0-t), and AUC(0-infinity) was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng center dot h/mL, and 120 ng center dot h/mL for test formulation and 12.7 ng/ml, 120 ng center dot h/mL, and 123 ng center dot h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng center dot h/mL, and 102 ng center dot h/mL for the test formulation and 3.80 ng/ml, 89.7 ng center dot h/mL, and 102 ng center dot h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng center dot h/mL, and 718 ng center dot h/mL for test formulation and 60.2 ng/ml, 648 ng center dot h/mL, and 702 ng center dot h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths or serious adverse events were reported.ConclusionsFixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets.

Automated summary

This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations in healthy Chinese subjects under fasting conditions. The results showed that the fixed dose combination achieved bioequivalence with reference to commercial tablets.